A 15-month-old boy, exclusively breastfed and rarely taken outdoors, has bowed legs and delayed walking. His mother did not take vitamin D during pregnancy. Results: calcium 2.10 mmol/L (8.4 mg/dL; reference 2.20-2.70), phosphate 0.95 mmol/L (2.9 mg/dL; age reference 1.20-2.10), alkaline phosphatase 1,180 U/L (age reference 150-420), intact PTH 21 pmol/L (198 ng/L; reference 1.6-6.9) and 25-hydroxyvitamin D 14 nmol/L (5.6 ng/mL; deficiency below 30 nmol/L). Creatinine is normal for his age. The diagnosis that best fits these results is:

Nutritional vitamin D deficiency rickets

X-linked hypophosphatemic rickets

Vitamin D-dependent rickets type 1A

Renal osteodystrophy from kidney failure

A 55-year-old man is admitted with vomiting, thirst and confusion. He takes several supplements bought online. Results: calcium 3.35 mmol/L [13.4 mg/dL] (2.15-2.55), PTH 0.8 pmol/L (1.6-6.9), PTHrP undetectable, 25-hydroxyvitamin D 620 nmol/L [248 ng/mL], creatinine 160 µmol/L. What is the most likely cause of his hypercalcemia?

Humoral hypercalcemia of malignancy

A 45-year-old woman has taken prescribed ergocalciferol (vitamin D2) 50,000 IU weekly for 12 weeks, and her pharmacist confirms she collects it. Her PTH has fallen from 12.5 to 5.0 pmol/L (1.6-6.9), but 25-hydroxyvitamin D by the laboratory's immunoassay has risen only from 26 to 30 nmol/L [10 to 12 ng/mL]. The most likely explanation is:

The assay under-detects 25-hydroxyvitamin D2

Poor absorption of the vitamin D from the gut

Excess conversion to 1,25-dihydroxyvitamin D

Failure of 25-hydroxylation in the liver

Vitamin D and bone metabolism

9 DOH Abu Dhabi (HAAD) lab licensing practice questions on Vitamin D and bone metabolism, part of Clinical Chemistry. The first 9 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

Question 1 · Hard
A 15-month-old boy, exclusively breastfed and rarely taken outdoors, has bowed legs and delayed walking. His mother did not take vitamin D during pregnancy. Results: calcium 2.10 mmol/L (8.4 mg/dL; reference 2.20-2.70), phosphate 0.95 mmol/L (2.9 mg/dL; age reference 1.20-2.10), alkaline phosphatase 1,180 U/L (age reference 150-420), intact PTH 21 pmol/L (198 ng/L; reference 1.6-6.9) and 25-hydroxyvitamin D 14 nmol/L (5.6 ng/mL; deficiency below 30 nmol/L). Creatinine is normal for his age. The diagnosis that best fits these results is:
1. AX-linked hypophosphatemic rickets
2. BVitamin D-dependent rickets type 1A
3. CRenal osteodystrophy from kidney failure
4. DNutritional vitamin D deficiency rickets
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Answer: D · Nutritional vitamin D deficiency rickets
Low calcium, low phosphate, very high alkaline phosphatase and a raised PTH are the pattern of calcipenic rickets with secondary hyperparathyroidism. The very low 25-hydroxyvitamin D, with exclusive breastfeeding, little sunlight and an unsupplemented mother, identifies nutritional vitamin D deficiency. In X-linked hypophosphatemic rickets the defect is renal phosphate wasting from excess FGF23, so calcium and 25-hydroxyvitamin D are normal and PTH is usually normal. Vitamin D-dependent rickets type 1A is a defect of renal 1-alpha-hydroxylase, so 25-hydroxyvitamin D is normal or high, and renal osteodystrophy needs a raised creatinine. With vitamin D and calcium treatment, alkaline phosphatase falls as the bones heal.
- A: XLH wastes phosphate through FGF23, with normal calcium and 25-hydroxyvitamin D.
- B: In 1-alpha-hydroxylase deficiency, 25-hydroxyvitamin D is normal or high, not very low.
- C: Creatinine is normal for age, so kidney failure is not the cause.
Question 2 · Easy
Which compound in the skin is converted to previtamin D3 by ultraviolet B light?
1. A7-Dehydrocholesterol
2. BCholecalciferol
3. CCalcidiol
4. DErgosterol
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Answer: A · 7-Dehydrocholesterol
UVB light opens a ring of 7-dehydrocholesterol in the skin to form previtamin D3, which body heat then converts to vitamin D3 (cholecalciferol). Covering clothing, darker skin, sunscreen and staying indoors in the hot months all reduce this, which is why deficiency is common in the UAE despite strong sunshine. Ergosterol from fungi and yeast is the precursor of vitamin D2. Normally most of the body's vitamin D comes from the skin rather than food.
- B: Cholecalciferol is the vitamin D3 formed from previtamin D3, not its precursor.
- C: Calcidiol is 25-hydroxyvitamin D, made later in the liver.
- D: Ergosterol, from fungi and yeast, is the precursor of vitamin D2 (ergocalciferol).
Question 3 · Easy
Vitamin D made in the skin or taken in the diet is first hydroxylated to 25-hydroxyvitamin D in the:
1. ASmall intestine
2. BKidney
3. CParathyroid glands
4. DLiver
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Answer: D · Liver
Vitamin D from the skin or diet is carried to the liver, where 25-hydroxylase (mainly CYP2R1) forms 25-hydroxyvitamin D (calcidiol). This step is not tightly regulated, so 25-hydroxyvitamin D reflects supply and is the form measured to assess status. The kidney's 1-alpha-hydroxylase then forms the active hormone, 1,25-dihydroxyvitamin D (calcitriol), under the control of PTH, phosphate and FGF23. Calcidiol has a half-life of about 2 to 3 weeks, compared with a few hours for calcitriol.
- A: The intestine absorbs vitamin D and responds to calcitriol; it does not 25-hydroxylate it.
- B: The kidney adds the 1-alpha hydroxyl group that makes calcitriol.
- C: The parathyroid glands make PTH, which stimulates the kidney step.
Question 4 · Hard
A 55-year-old man is admitted with vomiting, thirst and confusion. He takes several supplements bought online. Results: calcium 3.35 mmol/L [13.4 mg/dL] (2.15-2.55), PTH 0.8 pmol/L (1.6-6.9), PTHrP undetectable, 25-hydroxyvitamin D 620 nmol/L [248 ng/mL], creatinine 160 µmol/L. What is the most likely cause of his hypercalcemia?
1. ASarcoidosis
2. BHumoral hypercalcemia of malignancy
3. CPrimary hyperparathyroidism
4. DVitamin D intoxication
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Answer: D · Vitamin D intoxication
Hypercalcemia with a suppressed PTH is PTH-independent, and a 25-hydroxyvitamin D far above about 375 nmol/L (150 ng/mL) identifies excess vitamin D intake as the cause. At such levels 25-hydroxyvitamin D itself activates the vitamin D receptor and displaces calcitriol from its binding protein, increasing gut absorption of calcium and bone resorption. Because vitamin D is stored in fat, the hypercalcemia can last for weeks after the supplement is stopped. High-dose products are easy to buy, so supplement use should be asked about in any unexplained hypercalcemia.
- A: Sarcoidosis raises calcitriol, with a normal 25-hydroxyvitamin D.
- B: Humoral hypercalcemia of malignancy is driven by PTHrP, which is undetectable here.
- C: Primary hyperparathyroidism gives a high or inappropriately normal PTH.
Question 5 · Hard
A 45-year-old woman has taken prescribed ergocalciferol (vitamin D2) 50,000 IU weekly for 12 weeks, and her pharmacist confirms she collects it. Her PTH has fallen from 12.5 to 5.0 pmol/L (1.6-6.9), but 25-hydroxyvitamin D by the laboratory's immunoassay has risen only from 26 to 30 nmol/L [10 to 12 ng/mL]. The most likely explanation is:
1. APoor absorption of the vitamin D from the gut
2. BThe assay under-detects 25-hydroxyvitamin D2
3. CExcess conversion to 1,25-dihydroxyvitamin D
4. DFailure of 25-hydroxylation in the liver
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Answer: B · The assay under-detects 25-hydroxyvitamin D2
Some 25-hydroxyvitamin D immunoassays recognize 25-hydroxyvitamin D2 less well than D3, so patients treated with ergocalciferol can appear to stay deficient. The fall in PTH shows that her vitamin D status has in fact improved. LC-MS/MS measures 25-hydroxyvitamin D2 and D3 separately and can confirm this. Laboratories should know how well their assay recovers D2, because high-dose ergocalciferol is still prescribed in many countries.
- A: Malabsorption would leave PTH high, but it has fallen into range.
- C: Conversion to calcitriol is tightly controlled and uses only a tiny fraction of the supply.
- D: Failed liver 25-hydroxylation is rare and would also leave PTH high.
Question 6 · Medium
A 32-year-old woman in Abu Dhabi who wears fully covering clothing has bone aches. Results: calcium 2.25 mmol/L (2.15-2.55), phosphate 0.76 mmol/L (0.81-1.45), creatinine 58 µmol/L (45-90), PTH 14.2 pmol/L (1.6-6.9), 25-hydroxyvitamin D 18 nmol/L [7 ng/mL] (sufficient above 50 nmol/L). The best interpretation is:
1. AHyperparathyroidism of chronic kidney disease
2. BNormocalcemic primary hyperparathyroidism
3. CSecondary hyperparathyroidism from vitamin D deficiency
4. DPseudohypoparathyroidism
Answer and explanation in LearnFree account
Question 7 · Hard
A 38-year-old woman has calcium 2.92 mmol/L [11.7 mg/dL] (2.15-2.55), PTH 0.9 pmol/L (1.6-6.9), PTHrP undetectable, 25-hydroxyvitamin D 62 nmol/L [25 ng/mL], a markedly raised 1,25-dihydroxyvitamin D and enlarged hilar lymph nodes on chest X-ray. Her hypercalcemia is most likely caused by:
1. APTH-related peptide from a lung tumor
2. BPTH excess from a parathyroid adenoma
3. CMacrophage 1-alpha-hydroxylase in granulomas
4. DToo much vitamin D from supplements
Answer and explanation in LearnFree account
Question 8 · Medium
A 25-hydroxyvitamin D result is 14 ng/mL. Using a conversion factor of 2.5, what is this in SI units?
1. A350 nmol/L
2. B5.6 nmol/L
3. C14 nmol/L
4. D35 nmol/L
Answer and explanation in LearnFree account
Question 9 · Medium
Which test best reflects a person's vitamin D status?
1. A25-hydroxyvitamin D
2. BTotal calcium
3. CParathyroid hormone
4. D1,25-dihydroxyvitamin D
Answer and explanation in LearnFree account

Vitamin D and bone metabolism

Which compound in the skin is converted to previtamin D3 by ultraviolet B light?

Vitamin D made in the skin or taken in the diet is first hydroxylated to 25-hydroxyvitamin D in the:

A 38-year-old woman has calcium 2.92 mmol/L [11.7 mg/dL] (2.15-2.55), PTH 0.9 pmol/L (1.6-6.9), PTHrP undetectable, 25-hydroxyvitamin D 62 nmol/L [25 ng/mL], a markedly raised 1,25-dihydroxyvitamin D and enlarged hilar lymph nodes on chest X-ray. Her hypercalcemia is most likely caused by:

A 25-hydroxyvitamin D result is 14 ng/mL. Using a conversion factor of 2.5, what is this in SI units?

Which test best reflects a person's vitamin D status?